Oligo-peptide I-C-F-6 inhibits hepatic stellate cell activation and ameliorates CCl4-induced liver fibrosis by suppressing NF-κB signaling and Wnt/β-catenin signaling
Oligo-peptide I-C-F-6 inhibits hepatic stellate cell activation and ameliorates CCl4-induced liver fibrosis by suppressing NF-κB signaling and Wnt/β-catenin signaling
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DOI：
10.1016/j.jphs.2018.01.003
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发表时间：
2018-03-01
影响因子：
3.5
通讯作者：
He, Songqi
中科院分区：
文献类型：
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作者：
Sun, Haitao;Chen, Guanxin;He, Songqi
寡肽I-C-F-6是一种对肝纤维化有作用的甲壳草提取物成分，但其作用机制尚不清楚。本研究探讨寡肽I-C-F-6是否通过抑制肝纤维化中重要的NF-kappa B和Wnt/ β -catenin信号传导来抑制肝纤维化。将大鼠随机分为5组：对照组（生理盐水）、CCl4、CCl4加寡聚肽I-C-F-6（0.12、0.24 mg/kg）、CCl4加秋水仙碱（0.11 mg/kg）。在这里，我们证明了寡肽I-C-F-6改善了CCl4诱导的肝损伤、炎症和肝纤维化。寡肽I-C-F-6在体内和体外也能抑制肝星状细胞（HSC）的活化，这是通过转化生长因子- β 1 （tgf - β 1）和α -平滑肌肌动蛋白（α - sma）的表达来评估的，α -平滑肌肌动蛋白是HSC活化的特异性标志物。寡聚肽I- c - f -6显著降低β -catenin、P- akt、phospho (P)-GSK-3 β、nuclear factor kappa B (NF-kappa B) P65、phospho-P65和I- kappa B激酶α / β (ikk - α / β)水平的表达和分布；体内和体外I κ pa b - α水平均升高。综上所述，这些结果表明寡肽I-C-F-6在肝纤维化动物模型中具有肝保护和抗纤维化作用，其机制可能与调节nf - κ B和Wnt/ β -catenin信号通路有关。(c) 2018年作者。由Elsevier B.V.代表日本药理学会制作和主办。这是一篇基于CC BY-NC-ND许可（http://creativecommons.org/licenses/by-nc-nd/4.0/）的开放获取文章。
Oligo-peptide I-C-F-6 is a Carapax trionycis extract component that has an effect on hepatic fibrosis, however, its mechanism of action is still unclear. This study investigated whether oligo-peptide I-C-F-6 could inhibit liver fibrosis by suppressing NF-kappa B and Wnt/beta-catenin signaling, which are important in liver fibrosis. HSC-T6 cells were treated with oligo-peptide I-C-F-6, and rats were divided randomly into five groups: control (saline), CCl4, CCl4 plus oligo-peptide I-C-F-6 (0.12 and 0.24 mg/kg), and CCl4 plus colchicine (0.11 mg/kg). Here, we demonstrated that oligo-peptide I-C-F-6 ameliorated liver injury, inflammation, and hepatic fibrogenesis induced by CCl4. Oligo-peptide I-C-F-6 also inhibited the activation of hepatic stellate cells (HSCs) in vivo and in vitro, as evaluated by the expression of transforming growth factor-beta 1 (TGF-beta 1) and alpha-smooth muscle actin (alpha-SMA), which is a specific marker of HSC activation. Moreover, oligo-peptide I-C-F-6 significantly reduced the expression and distribution of beta-catenin, P-AKT, phospho (P)-GSK-3 beta, nuclear factor kappa B (NF-kappa B) P65, phospho-P65, and I kappa B kinase alpha/beta (IKK-alpha/beta) levels; additionally, I kappa B-alpha level was elevated both in vivo and in vitro. Together, these results indicate that oligo-peptide I-C-F-6 has hepatoprotective and anti-fibrotic effects in animal models of liver fibrosis, the mechanism of which may be related to modulating NF-kappa B and Wnt/beta-catenin signaling. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).